Honghua Ruyi Pill, a compound herbal medicine, improves endometriosis-related dysmenorrhea: A multicenter randomized, double-blind, placebo-controlled trial

Abstract

Background: Endometriosis is an estrogen-dependent, progesterone-resistant gynecological disorder, with dysmenorrhea being the most common manifestation.

Objective: This study evaluates the efficacy and safety of the Tibetan herbal medication Honghua Ruyi Pill (HHRY) in managing endometriosis-related dysmenorrhea.

Design, setting, participants and interventions: This is a multi-center, randomized, placebo-controlled, double-blinded clinical trial conducted in seven hospitals in China from July 2021 to January 2023. A total of 164 patients with endometriosis and moderate or severe dysmenorrhea (visual analog scale [VAS] score ≥ 4) were assigned to the treatment or placebo group in a 1:1 ratio by block randomization. Patients received HHRY or placebo twice a day for three consecutive menstrual cycles (MCs) and were followed up for three MCs after stopping the medication.

Main outcome measures: Primary outcomes were VAS score of the maximum (VAS_max) of dysmenorrhea, endometriosis health profile-5 (EHP-5) score, and 5-level EuroQoL 5-dimension version (EQ-5D-5L) score. Secondary outcomes were VAS_max of non-menstrual pelvic pain, days of leave taken, emergent use of nonsteroidal anti-inflammatory drugs (NSAIDs) and changes in uterine, cyst and nodule sizes. Safety profiles were assessed based on adverse events, vital signs, serology markers, urinalysis, and liver and kidney function indicators.

Results: VAS_max of dysmenorrhea, EHP-5 score, EQ-5D-5 L score, and VAS_max of non-menstrual pelvic pain were significantly lower in the HHRY group compared to the placebo group at the final follow-up (3.00 vs 5.50, P < 0.001; 4.00 vs 8.00, P < 0.001; 4.00 vs 9.00, P < 0.001; 0.00 vs 1.00, P < 0.001; respectively). The emergent use of NSAIDs for breakthrough pain showed no significant difference between groups (P > 0.999), but the number of patients who had taken time off was significantly different (5.00 vs 14.00, P = 0.028). Sonographic evaluations indicated no significant change in uterine size (P = 0.183) but showed a significant reduction in cyst size (2.09 cm vs 0.20 cm, P = 0.027, sum of 3 diameters of cysts) and nodule size (0.70 cm vs 0.00 cm, P < 0.001, maximum nodule diameter). Safety analysis showed no significant difference in the incidence of adverse events between groups (18.85% vs 28.05%, P = 0.059).

Conclusion: HHRY can improve dysmenorrhea, chronic pelvic pain, and quality of life in patients with endometriosis. It has a good overall safety profile, and a 3-month treatment can maintain its effects for at least 3 months after the last dose. HHRY may be considered as a new therapeutic option for treating endometriosis-related dysmenorrhea.

Trial registration: Trial registration at ClinicalTrials.gov with registration number: NCT04942015. Please cite this article as: Han M, Liang XF, Gao J, Wang Y, Cao LX, Wang BJ, Wang Y, Zerang Z, Liu JP, Du HL. Honghua Ruyi Pill, a compound herbal medicine, improves endometriosis-related dysmenorrhea: A multicenter randomized, double-blind, placebo-controlled trial. J Integr Med. 2026; 24(2):182-191.

Keywords: Dysmenorrhea; Endometriosis; Herbal medicine; Honghua Ruyi Pill; Non-menstrual pelvic pain; Quality of life.